The secretogranin II gene is a signal integrator of glutamate and dopamine inputs. (24th October 2013)

• Record Type: Journal Article
• Authors: Iwase, Katsuro; Ishihara, Akinori; Yoshimura, Shuntaro; Andoh, Yoshio; Kato, Masaki; Seki, Naohiko; Matsumoto, Eriko; Hiwasa, Takaki; Muller, Dominique; Fukunaga, Kohji; Takiguchi, Masaki
• Is Part Of: Journal of neurochemistry. Volume 128:Number 2(2014:Jan.)
• Page Start: 233
• Page End: 245
• Publication Date: 2013-10-24
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12467
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc12467-abs-0001"> <title>Abstract</title> <p>Cooperative gene regulation by different neurotransmitters likely underlies the long‐term forms of associative learning and memory, but this mechanism largely remains to be elucidated. Following cDNA microarray analysis for genes regulated by Ca<sup>2+</sup> or cAMP, we found that the secretogranin II gene (<italic>Scg2</italic>) was cooperatively activated by glutamate and dopamine in primary cultured mouse hippocampal neurons. The Ca<sup>2+</sup> chelator 1, 2‐bis(2‐aminophenoxy)ethane‐<italic>N</italic>, <italic>N</italic>, <italic>N</italic>', <italic>N</italic>'‐tetraacetic acid acetoxymethyl ester (BAPTA‐AM) and the mitogen‐activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 prevented <italic>Scg2</italic> activation by glutamate or dopamine; thus, the Ca<sup>2+</sup>/MEK pathway is predicted to include a convergence point(s) of glutamatergic and dopaminergic signaling. Unexpectedly, the protein kinase A inhibitor KT5720 enhanced <italic>Scg2</italic> activation by dopamine. The protein‐synthesis inhibitor cycloheximide also enhanced <italic>Scg2</italic> activation, and the proteasome inhibitor ZLLLH diminished the KT5720‐mediated augmentation of <italic>Scg2</italic> activation. These results are concordant with the notion that dopaminergic input leads to accumulation of a KT5720‐sensitive transcriptional repressor, which is short‐lived because of rapid degradation by proteasomes. This repression pathway may effectively limit the time window permissive to <italic>Scg2</italic> activation by in‐phase glutamate and dopamine inputs via the Ca<sup>2+</sup>/MEK pathway. We propose that the regulatory system of <italic>Scg2</italic> expression is equipped with machinery that is refined for the signal integration of in‐phase synaptic inputs. <boxed-text content-type="graphic" id="jnc12467-blkfxd-0001" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg3zxq037n" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> <p>We proposed hypothetical mechanism for the regulation of the secretogranin II gene as a signal integrator of glutamate and dopamine inputs. Glutamate or dopamine activates the Ca<sup>2+</sup>/MEK/ERK pathway, which thus contributes to the signal integration. Concurrently, activation of the PKA inhibitor KT5720‐sensitive pathway by dopamine leads to accumulation of the repressor protein <italic>X</italic> that is otherwise susceptible to proteasome degradation. This repression system may determine the time window permissive to the cooperative activation by in‐phase glutamate and dopamine inputs.</p> </abstract>